Title:MiRNAs Overexpression and Their Role in Breast Cancer: Implications
for Cancer Therapeutics
Volume: 24
Issue: 6
Author(s): Sau Har Lee*, Chu Xin Ng, Sharon Rachel Wong and Pei Pei Chong
Affiliation:
- School of Biosciences, Faculty of Health and Medical Sciences, Taylor’s University, Subang Jaya, Selangor,
Malaysia
- Centre for Drug Discovery and Molecular Pharmacology (CDDMP), Faculty of Health and Medical Sciences,
Taylor’s University, Subang Jaya, Selangor, Malaysia
Keywords:
Cancer therapeutic, anti-sense microRNA, microRNA delivery, breast cancer, therapeutic microRNA, oncogenic microRNA.
Abstract: MicroRNAs have a plethora of roles in various biological processes in the cells and
most human cancers have been shown to be associated with dysregulation of the expression of miRNA
genes. MiRNA biogenesis involves two alternative pathways, the canonical pathway which requires
the successful cooperation of various proteins forming the miRNA-inducing silencing complex
(miRISC), and the non-canonical pathway, such as the mirtrons, simtrons, or agotrons pathway,
which bypasses and deviates from specific steps in the canonical pathway. Mature miRNAs
are secreted from cells and circulated in the body bound to argonaute 2 (AGO2) and miRISC or
transported in vesicles. These miRNAs may regulate their downstream target genes via positive or
negative regulation through different molecular mechanisms. This review focuses on the role and
mechanisms of miRNAs in different stages of breast cancer progression, including breast cancer
stem cell formation, breast cancer initiation, invasion, and metastasis as well as angiogenesis. The
design, chemical modifications, and therapeutic applications of synthetic anti-sense miRNA oligonucleotides
and RNA mimics are also discussed in detail. The strategies for systemic delivery
and local targeted delivery of the antisense miRNAs encompass the use of polymeric and liposomal
nanoparticles, inorganic nanoparticles, extracellular vesicles, as well as viral vectors and viruslike
particles (VLPs). Although several miRNAs have been identified as good candidates for the design
of antisense and other synthetic modified oligonucleotides in targeting breast cancer, further efforts
are still needed to study the most optimal delivery method in order to drive the research beyond
preclinical studies.
